Naringenin prevents ischaemic stroke damage via anti-apoptotic and anti-oxidant effects

被引:101
作者
Wang, Kaihua [1 ,2 ]
Chen, Zhenzhen [3 ]
Huang, Jianmin [2 ]
Huang, Longjian [2 ]
Luo, Ning [2 ]
Liang, Xiulin [2 ]
Liang, Mingkun [2 ]
Xie, Wei [1 ,4 ,5 ]
机构
[1] Southern Med Univ, Guangzhou, Peoples R China
[2] Guangxi Univ Chinese Med, RuiKang Hosp, Dept Neurol, Nanning, Peoples R China
[3] Guangxi Univ Chinese Med, Nanning, Peoples R China
[4] Southern Med Univ, Sch Tradit Chinese Med, Guangzhou, Guangdong, Peoples R China
[5] Southern Med Univ, Nanfang Hosp, Dept Tradit Chinese Med, Guangzhou, Guangdong, Peoples R China
关键词
apoptosis; middle cerebral artery occlusion; naringenin; Nrf2; oxidative stress; oxygen and glucose deprivation/reperfusion; OXIDATIVE STRESS; FLAVONOIDS; HESPERETIN; INJURY; NRF2;
D O I
10.1111/1440-1681.12775
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Apoptosis and oxidative stress are considered to be the major factors associated with the development and progression of many ischaemic cerebrovascular diseases. Naringenin (NAR) is an abundant flavanone in citrus plants and has been found to exhibit anti-oxidant, anti-carcinogenic and anti-apoptotic effects. This study aimed to investigate the anti-apoptotic and anti-oxidant effects of naringenin on ischaemic stroke. In vitro, cortical neuron cells isolated from the brains of neonatal Sprague-Dawley rats were randomly divided into control, oxygen and glucose deprivation/reperfusion (OGD/Rep), NAR-L, NAR-M and NAR-H groups. MTT and RT-PCR were used for cell proliferation and apoptosis-related proteins analyses. The effects of NAR on the Nrf2 signalling pathway were investigated using transfection approaches. Differences in mitochondrial dysfunction were analyzed by flow cytometry. In vivo, middle cerebral artery occlusion (MCAO) model was prepared and neurological defects and the brain wet/dry (W/D) ratio were assessed and recorded; apoptosis was measured based on the TUNEL assay. Additionally, biochemical indices were detected both in vitro and in vivo. NAR promoted cortical neuron cell proliferation, inhibited apoptosis and oxidative stress, and regulated the localization of Nrf2 protein (P<.05). Furthermore, silencing and overexpression of Nrf2 affected cortical neuron cell proliferation and apoptosis (P<.05). In vivo, NAR could alleviate cerebral oedema, improve neurological defects, and reduce apoptosis and oxidative stress (P<.05). These findings demonstrated that NAR could reduce apoptosis and oxidative stress and that Nrf2 signalling pathway is involved in this regulatory process. NAR has health-promoting properties because of its anti-apoptotic and anti-oxidant effects in cases of ischaemic stroke.
引用
收藏
页码:862 / 871
页数:10
相关论文
共 30 条
[1]
Interactions of Oxidative Stress and Neurovascular Inflammation in the Pathogenesis of Traumatic Brain Injury [J].
Abdul-Muneer, P. M. ;
Chandra, Namas ;
Haorah, James .
MOLECULAR NEUROBIOLOGY, 2015, 51 (03) :966-979
[2]
Targeting the Nrf2-Keap1 antioxidant defence pathway for neurovascular protection in stroke [J].
Alfieri, Alessio ;
Srivastava, Salil ;
Siow, Richard C. M. ;
Modo, Michel ;
Fraser, Paul A. ;
Mann, Giovanni E. .
JOURNAL OF PHYSIOLOGY-LONDON, 2011, 589 (17) :4125-4136
[3]
Molecular pathways to neurodegeneration [J].
Bossy-Wetzel, E ;
Schwarzenbacher, R ;
Lipton, SA .
NATURE MEDICINE, 2004, 10 (07) :S2-S9
[4]
Candelario-Jalil E, 2009, CURR OPIN INVEST DR, V10, P644
[5]
Antioxidant and prooxidant behavior of flavonoids: Structure-activity relationships [J].
Cao, GH ;
Sofic, E ;
Prior, RL .
FREE RADICAL BIOLOGY AND MEDICINE, 1997, 22 (05) :749-760
[6]
Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats [J].
Chen, JL ;
Sanberg, PR ;
Li, Y ;
Wang, L ;
Lu, M ;
Willing, AE ;
Sanchez-Ramos, J ;
Chopp, M .
STROKE, 2001, 32 (11) :2682-2688
[7]
Nrf2-induced antioxidant Protection: A Promising target to counteract ROS-mediated damage in neurodegenerative disease? [J].
de Vries, Helga E. ;
Witte, Maarten ;
Hondius, David ;
Rozermuller, Annemieke J. M. ;
Drukarch, Benjamin ;
Hoozemans, Jeroen ;
van Horssen, Jack .
FREE RADICAL BIOLOGY AND MEDICINE, 2008, 45 (10) :1375-1383
[8]
Review of the flavonoids quercetin, hesperetin naringenin. Dietary sources, bioactivities, and epidemiology [J].
Erlund, I .
NUTRITION RESEARCH, 2004, 24 (10) :851-874
[9]
Mitochondria and apoptosis [J].
Green, DR ;
Reed, JC .
SCIENCE, 1998, 281 (5381) :1309-1312
[10]
17β-Estradiol prevents cell death and mitochondrial dysfunction by an estrogen receptor-dependent mechanism in astrocytes after oxygen-glucose deprivation/reperfusion [J].
Guo, Jiabin ;
Duckles, Sue P. ;
Weiss, John H. ;
Li, Xuejun ;
Krause, Diana N. .
FREE RADICAL BIOLOGY AND MEDICINE, 2012, 52 (11-12) :2151-2160